The human knee is an important and complex joint comprising three spatially inter-related bones (the femur, tibia and patella), ligaments and cartilaginous structures all of which interact to create a variety of motions. The surfaces of the knee bones within the joint are covered with articular cartilage. This important surface allows the bones to smoothly glide against each other without causing damage to the bone. The meniscus, a C-shaped cartilage cushion sits between the articular cartilage surfaces of the bone and acts as a shock absorber by distributing weight and so improves the overall stability of the knee joint. Each knee joint has a medial and lateral meniscus which is composed of fibrochondrocytes, proteoglycans and an extra-cellular matrix of collagen and elastin fibres. When menisci are damaged through injury, disease or inflammation arthritic changes can develop in the knee joint with consequent swelling, pain and/or loss of knee joint function in the affected individual. Whilst it is possible to repair a torn meniscus, a meniscus that is severely damaged or has an extensive tear may have to be removed.
Since joint cartilage in adults does not naturally regenerate to a significant degree once it is destroyed, damaged adult menisci have historically been treated by a variety of surgical interventions including removal and replacement with prosthetic devices. In older patients, a knee joint replacement is often the preferred option. However, for younger individuals (those under 50 or 55 years old) the alternative to replacing the entire joint is a meniscal transplant which uses either prosthetic menisci or donor tissue to replace the damaged meniscus.
A problem associated with the use of donor tissue for meniscal replacement is that the meniscus is a dense fibrocartilagenous tissue impregnated throughout with fibrochondrocytes which are the cells responsible for synthesis, maintenance and repair of the extracellular matrix. The human medial meniscus is approximately 4.5 mm in length and the lateral meniscus is approximately 3.5 mm in length, the thickness of each range from 25 to 35 mm (porcine values are similar to those of human menisci.) Because the meniscus is a thick and dense tissue with cells located throughout and especially around the microvasculature it is extremely difficult to decellularise, especially at the central regions, which in turn means that it is difficult to prepare an immunologically inert or decellularised tissue for transplantation and so there is a risk of rejection. In other words there is low biocompatibility and a high risk of the host having an immunological reaction from either a heterograft or xenograft.
In order to provide an acellular biocompatible meniscal implant, artificial meniscal prostheses have been developed. However, a problem associated with an artificial meniscal prosthesis is that it not as robust as natural meniscal tissue and also it is deficient in the elastic properties of the natural menisci consequently such prostheses are not as effective at shock absorption as the natural material.
A method that could effectively decellularise donor meniscal tissue would offer immediate benefit to the treatment of individuals requiring a meniscal implant/transplant.